The Interface Between Anesthesia and Immunomodulation with Implications for Perioperative Inflammation and Cancer Recurrence

Abstract

The perioperative period is a critical window characterized by profound surgical stress and inflammation, which can induce significant immunosuppression. This state is hypothesized to facilitate the survival and proliferation of residual cancer cells, thereby increasing the risk of recurrence and metastasis. Anesthetic techniques, as integral components of perioperative care, are increasingly recognized as active modulators of this complex immune response rather than immunologically neutral agents. This narrative review aims to synthesize and critically evaluate the current evidence on the interface between various anesthetic and analgesic techniques and their immunomodulatory effects. The primary focus is to elucidate the implications for perioperative inflammation and long-term oncological outcomes, specifically cancer recurrence. A comprehensive literature search was conducted across major scientific databases, including PubMed, Scopus, and Web of Science. The review includes relevant preclinical (in vitro and in vivo) and clinical studies investigating the impact of volatile anesthetics, propofol-based total intravenous anesthesia (TIVA), regional anesthesia, and opioids on key components of the innate and adaptive immune systems. A consistent pattern emerges from preclinical data, indicating that volatile anesthetics and opioids tend to exert immunosuppressive effects by inhibiting the cytotoxicity of natural killer (NK) cells and T lymphocytes while promoting regulatory T cells (Tregs). In contrast, propofol and regional anesthetic techniques (via opioid-sparing) appear to be immune-sparing or even protective. However, this strong biological rationale has not been consistently translated into definitive outcomes in large-scale clinical trials, which have yielded conflicting results, likely due to significant clinical heterogeneity and confounding factors. The choice of anesthesia is an active immunomodulatory intervention with plausible effects on cancer recurrence. Despite inconclusive clinical data, the compelling biological evidence supports the adoption of a multimodal immunoprotective strategy. Combining propofol-based TIVA with regional anesthesia and opioid-sparing analgesia represents a rational approach to mitigate perioperative immunosuppression and may potentially improve long-term outcomes for patients undergoing cancer surgery